This resubmitted application is for a renewal to CA59005, "Aspirin/Folate Prevention of Large Bowel Polyps," a randomized, double blind, placebo-controlled trial to evaluate the effectiveness of aspirin and/or folate supplementation in preventing adenomas of the large bowel among subjects with a history of these tumors. The study compared two aspirin doses (81 mg or 325 mg dally) versus placebo and folate (1 mg daily) versus placebo in a factorial design. Subjects underwent colonoscopic follow-up 36 months after study entry and were invited to continue randomized folate treatment and/or follow-up during an additional colonoscopic surveillance cycle. The trial showed a significant benefit with low dose aspirin. Results for folate treatment have not yet been reported; unblinded analyses will be sent in a confidential letter from the chair of the study's Safety and Data Monitoring Committee to the executive secretary of the study section. We are now making plans to discontinue the extended folate treatment. With the funds sought in this application, we propose to complete observational follow-up of subjects for one surveillance cycle after the end of randomized aspirin treatment and to conduct molecular studies of colorectal carcinogenesis and aspirin chemoprevention. These investigations will involve measurement of proliferation, apoptosis, differentiation, inflammation and Wnt signaling in adenomas that were diagnosed at baseline and during aspirin treatment. We also propose to conduct a combined folate analysis with the clinical trial recently completed by the Harvard School of Public Health, with a focus on the randomized assessment of the effect of folate supplementation among individuals who regularly consume alcohol. Our scientific aims are: 1) to assess the association between randomized assignment to aspirin or placebo and adenoma risk in the 3 to 5 year period after the end of randomized aspirin treatment, taking into account NSAID use during this later period, 2) to assess the effect of randomized aspirin treatment on the molecular markers in adenomas occurring while on treatment, 3) to study the molecular epidemiology of the molecular markers in baseline adenomas and 4) to assess the effect of folate treatment on adenoma occurrence among study subjects who drink alcohol. [unreadable] [unreadable]